Keratoprosthesis

Core Messages

■Despite the widespread use of standard keratoplasty, there continues to be a worldwide need for alternative therapies due to:

(a)Substantial rates of graft failure on long-term follow-up

(b)Poor prognosis in patients with underlying inflammation or chemical burns

(c)Limited access to resources including donor tissue

■Experience with keratoprosthesis (Kpro) has grown rapidly over the past two decades, and has resulted in improved outcomes and decreased complications for a large number of patients.

■A key lesson learned is that long-term prognosis is linked to underlying diagnosis.

■Kpro patients should be divided into two categories and examined separately:

(a) In patients who have experienced failed grafts for corneal dystrophies, trauma, and infection, but lack underlying severe ocular inflammation, Kpro has yielded promising results in terms of device retention and improved visual acuity.

(b)In patients with cicatrizing autoimmune diseases and chemical burns, the prognosis for Kpro has been more guarded.

■A variety of Kpro designs are currently in use, and may have specific applications based on underlying patient subtype.

■Assessment of current and future Kpro technology should account for this prognostic hierarchy.

■Experimental “biologic” designs that aim to better integrate Kpro material with corneal tissue wcomplications, but are yet to be proven.

10.1Introduction

An estimated eight million people worldwide are blind due to corneal disease [53], making it the third leading cause of blindness after cataract and glaucoma [55]. Since the early twentieth century, keratoplasty has offered hope to many people suffering from corneal blindness due to a variety of conditions. In fact, keratoplasty has become the most frequently performed organ transplant worldwide [17]. However, keratoplasty is not without its limitations. Graft failure remains a persistent problem [58]. In a large retrospective study, grafts for all causes remained clear in only 70% of cases after 5 years [6, 58]. Examined separately, regrafts fare even worse. Bersudsky et al. found that only 20% of first regrafts were clear after 5 years, while all repeat regrafts had failed over that same period [5]. In addition, the prognosis for standard keratoplasty is significantly worse in certain “high-risk” diagnostic categories including autoimmune conditions and chemical burns [6, 36, 55, 56]. Finally, in large parts of the world, keratoplasty is

unfeasible due to lack of health resources or cultural impediments, resulting in an inadequate supply of donor corneas [10]. Given these limitations, the need for a safe and effective keratoprosthesis (Kpro) as an alternative to keratoplasty remains strong.

Th e concept of Kpro has captured the attention of scientists and physicians for more than 200 years [43]. For a detailed history of Kpro, the reader is referred to previous review articles on this subject [12, 33]. Development of an effective Kpro was initially slow due to significant early and late-stage complications, often resulting in loss of the eye. However, over the past several decades, renewed interest and improved technology have allowed great strides to be made. In 1992, there were only 15 Kpro operations attempted in the United States [13]. In 2008, the corresponding number was over 800. While this number is small compared to the approximately 100,000 standard keratoplasties performed worldwide per year [13], this rapid expansion in experience has brought forth key lessons for the present and future use of Kpro as a viable therapy for severe corneal opacities.

13810 Keratoprosthesis

10.2Prognostic Hierarchy

One key principle that has emerged from recent experience with Kpro is that prognosis is clearly linked to diag- 10 nosis. A retrospective study by Yaghouti et al. [56] demonstrated the existence of a prognostic hierarchy among diagnostic categories for patients undergoing Boston Kpro surgery. Eyes with prior graft failure from nonautoimmune conditions (dystrophies, degenerations, or viral/bacterial infections) fared best, with 83% of those achieving better than 20/200 vision and maintaining it after 2 years, followed by ocular cicatrizing pemphigoid (OCP) (72%), chemical burns (64%), and StevensJohnson syndrome (SJS) (33%) [52]. Subsequent studies of Boston Kpro have confirmed consistently better outcomes among patients with nonautoimmune graft failure [7, 8, 59]. In contrast, patients with underlying autoimmune conditions and chemical burns have been shown to have worse outcomes and increased complications [8, 41, 59]. In a review of 227 patients receiving either osteoodonto keratoprosthesis (OOKP) or tibial keratoprosthesis (TKpro), Michael et al. found that primary diagnosis was the only significant factor associated with anatomical retention, with OCP having the worst prognosis [37].

Despite continued advances in Kpro materials and technique, options for these high-risk patients remain limited. It has become clear that Kpro patients should be separated into two broad subtypes, and that experience with Kpro falls along these two lines.

10.3Defining Patient Subtypes

10.3.1Patient Subtype A: The Noninflamed Eye

Th e first subtype consists of patients undergoing Kpro who lack significant history of ocular inflammation, and have normal blink mechanism and tear secretion. These patients have experienced graft failure with underlying diagnoses such as dystrophy, infection, trauma, aphakic/ pseudophakic bullous keratopathy [7, 13, 56, 59].

10.3.2Patient Subtype B: The Inflamed Eye

Th e second subtype consists of patients with acute and/or chronic inflammation due to underlying cicatrizing autoimmune disorders. Conditions such as SJS, OCP, graft- vs.-host disease (GVHD), and severe uveitis often lead to severe ocular surface damage due to destruction of limbal stem cells, corneal neovascularization, stromal scarring, and conjunctival fibrosis [41, 46, 49]. Patients with

chemical burns were initially considered high risk due to increased rates of endophthalmitis, corneal melt, retinal detachment, and glaucoma [56]. Although recent studies have suggested that outcomes in patients with chemical burns may be improving [7, 21, 59], these patients should still be approached with caution.

10.4Experience with Kpro in Patient Subtype A

Th ere is a growing body of data showing that patients who lack a significant history of ocular inflammation experience good outcomes after Kpro. Given that 15% of all keratoplasties in the U.S. are performed for graft failure, and that subsequent regrafts get progressively worse [5], Kpro should be considered as a viable alternative to further keratoplasty in these patients [15, 35].

10.4.1Boston Type 1 Kpro

Th e most commonly implanted device in the U.S. and worldwide is the Boston Type 1 Kpro. The Boston Kpro was approved by the FDA for patient use in 1992. This device is based on a “collar-button” design in which a central optical stem is stabilized by a front and back plate, all of which are made of poly (methyl methacrylate) (PMMA, Fig. 10.1). Donor corneal tissue is sandwiched between the front and back plates and then used as a carrier (Fig. 10.2). Technical details regarding its implantation have been reported elsewhere [11, 14, 15]. In a multicenter prospective study examining outcomes from 141 Boston Type 1 KPro surgeries, patients with preoperative diagnosis of noncicatrizing graft failure demonstrated BCVA ³20/200 in 90% and anatomic retention in 97% at a median follow-up of 8.5 months [59]. Ciolino et al. have subsequently reported a retention rate of 91.6% after extending the average follow-up to 13 months [8]. Eightythree percent of patients had preoperative diagnoses of graft rejection, chemical injury, or aphakic/pseudophakic bullous keratopathy. In a longer-term study of 30 eyes with average follow-up of 19 months, Bradley et al. found postoperative BCVA ³20/200 in 77% of eyes and 83.3% device retention [7]. In their single-surgeon series of 57 Boston Type 1 Kpro implantations, the largest to date, Aldave et al. report an 84% retention rate at an average follow-up of 17 months [1]. Of the patients for whom VA was checked postoperatively, BCVA was ³20/ 100 in 67% (30/45) at 6 months, 75% (21/28) at 1 year, and 69% (9/13) at 2 years. Although Kpro is typically reserved for patients with repeat graft failure, eight eyes in this cohort had no

history of prior corneal surgery. With a 100% retention rate in these eight eyes and postoperative BCVA ³20/80 in seven of eight eyes at an average follow-up of 22 months, the authors suggest that Kpro should be considered as the initial procedure in certain cases of visually significant corneal limbal stem cell deficiency. Prior dreaded complications of Boston Kpro surgery such as endophthalmitis have been reduced or eliminated due to improved technique and postoperative management including the use of life-long prophylactic antibiotic drops [13, 27]. Currently, the primary limitations to meaningful

recovery of vision are: end-stage glaucoma, retinal detachment, and age-related macular degeneration [14, 59, 40].

10.4.1.1Pediatric Application of Boston Type 1 Kpro

Another major advance has been the application of the Boston Type 1 Kpro in the pediatric population. The treatment of pediatric corneal opacity by standard keratoplasty renders patients at high risk for deprivation and

Fig. 10.2 (a) Clinical photo of osteo-odonto keratoprosthesis (OOKP).(b)Schematicofosteo-odontokeratoprosthesis(OOKP). Courtesy of Lippincott Williams & Wilkins (K Hille, et al. Cornea 2005 Nov; 24 (8): 895-908.)

remains promising. Limitations to OOKP include the complexity of the procedure involving multiple surgical specialties, and the need for the patient to donate a healthy, rooted tooth. Hille et al. found that one-third of patients referred to them for Kpro did not have a suitable tooth [24].

10.5.2Boston Type 2 Kpro

A slightly modified version of the Boston Type 1 Kpro was developed to improve outcomes in patients with severe ocular surface disease secondary to underlying inflammation. The Boston Type 2 Kpro is similar in design to the Type 1 except for the addition of a 2-mm anterior nub to the optical stem, which is meant to penetrate through the lid skin after concurrent, permanent tarsorraphy. In theory, protecting the ocular surface from drying by tarsorraphy reduces the rate of tissue melt [13]. Sayegh et al. conducted a retrospective study of 16 eyes with SJS undergoing Boston Kpro surgery [46]. Ten eyes (63%) underwent Type 2 surgery, and the rest Type I. Fifty percent of eyes had VA of 20/200 or better after 5 years. There were no spontaneous extrusions of the implant in this cohort. However, aqueous leakage necessitated the replacement of the device in two Type 2 eyes.

10.6Other Kpro Designs

10.6.1Pintucci Kpro

Th e Pintucci Kpro consists of an optical cylinder made of PMMA fixed to a woven Dacron membrane skirt, which allows for tissue in-growth. Pintucci et al. initially reported their results in 20 patients, 60% of whom suffered from mucous membrane pemphigoid [45]. At a mean follow-up of 58.9 months, there were two cases of device extrusion and one case of endophthalmitis. Thirtyfive percent of patients had BCVA >20/40. A more recent study of 31 Indian patients found no device extrusions at a mean follow-up of 3.2 years. However, only 6.5% of these patients achieved BCVA >20/40 [35].

10.6.2Seoul-Type Kpro

Th e Seoul-type Kpro (S-Kpro) utilizes an optic and skirt, but has additional haptics to increase postimplantation biomechanical stability. The device is anchored to the patient’s eye both by suturing the skirt to the cornea and by attachment of the additional haptics onto the sclera. Lee et al. reported their results in nine patients, six of whom had a diagnosis of SJS and one with OCP [28]. While they report a 66.7% anatomic retention rate at 68 months, all devices developed corneal melt leading to full exposure of the skirt, and four devices needed to be exchanged. All four eyes requiring Kpro exchange subsequently developed retinal detachments. Visual acuity of finger counting or higher was maintained for a mean 31.6 months [28].

10.6.3 Worst-Singh Kpro

Also known as the “champagne cork” Kpro, this device consists of a hood, anticonical PMMA shaft, and stainlesssteel loops which secure the hood to the sclera. The Worst-

142 10 Keratoprosthesis

Singh Kpro is implanted either in the center of the cornea or as a paralimbal scleral window [2]. While this device is currently utilized in India, primarily by Singh and col-

leagues, long-term outcomes data are not available.

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10.6.4Russian/Ukrainian Experience

It has been estimated that over 2,000 Kpro procedures have been done at the Fyodorov Institute in Moscow, the Filatov Institute in Odessa, and other centers across the former Soviet Union [26]. Yakimenko reported on 502 cases using their design of a central PMMA optical core and tantalum-titanium alloy haptics [57]. Eyes (51.5%) had a primary diagnosis of chemical burn. Long-term results demonstrated an extrusion rate of 12.1%, and approximately 48% of eyes achieved 20/200 vision or better. Yakimenko reported that improved surgical techniques and implants have lowered the extrusion rate to approximately 3.5%. However, subsequent data regarding the design, implementation, and outcomes of Kpro from this and other centers has been very limited.

10.7New Directions in Kpro Research

New research is focusing on ways to “biointegrate” Kpro with one or more layers of the cornea. According to Ciolino, integration with the corneal epithelium could theoretically stabilize the tear film and offer a barrier to infection, while stromal integration could offer improved structural stability and greater retention [9]. Several research groups are developing materials and methods for enhancing the biologic compatibility of Kpro.

10.7.1Hydroxyapatite Biologic Haptics

Success with autologous bone in OOKP and TKP has led to interest in other materials with similar properties to be used as Kpro haptics. Made of phosphate and calcium, hydroxyapatite has a similar mineral composition to both bone and teeth, and is frequently used as a bone substitute within the orbit [4]. In other studies, hydroxyapatite has been found to have superior keratocyte proliferation and adhesion over other materials currently used as Kpro haptics [36]. Leon et al. have developed a Kpro which utilizes a Coralline hydroxyapatite skirt to stabilize a central optic [29]. Their HAKpro has demonstrated fibrovascular tissue in-growth when implanted into rabbits. Although hydroxyapatite has promising biocompatibility profile, it is

inherently brittle and rigid. Another group has combined porous nano-hydroxyapatite with hydrogel to create a Kpro haptic [19]. Preliminary results in rabbits show in-growth of host tissue, deposition of collagen, and vascularization in the skirt material without intrastromal inflammation.

10.7.2Biologic Coatings

Other researchers have focused on improving in-growth and biocompatibility of corneal epithelial cells with Kpro materials. While most current Kpro haptic materials are inert and noncell-adhesive, coating these synthetic materials with bio-active extracellular matrix proteins may stimulate epithelial proliferation and adhesion. Several groups have found success with fibronectin, laminin, and collagen in encouraging epithelial cell growth on synthetic materials [42, 44, 48]. Sweeney et al. found collagen I, collagen IV, and laminin to support consistent multilayered epithelialization of synthetic material implanted into rabbit eyes. In collagen I-coated implants, they observed formation of a basement-membranes and adhesion complexes [48].

10.7.3Biologic Sca olds and Enhanced Hydrogels

Other groups have furthered the development of hydrogel technology first seen in clinical use with the AlphaCor Kpro. Fabrications have varied from collagen-based copolymers [20, 25] to interpenetrating polymer networks (IPN) [38]. These enhanced hydrogels are intended to support not only peripheral tissue integration but also corneal epithelialization and diffusion of bioactive substances such as glucose [38]. Results in vitro have so far been promising. Myung et al. demonstrated good retention, optical clarity, and multilayering of corneal epithelium of a poly(ethylene glycol)/poly(acrylic acid) (PEG/ PAA) IPN implanted intrastromally in rabbit corneas [39]. This group has also fabricated a single-piece keratoprosthesis (the “Stanford Kpro”), composed entirely of a PEG/PAA IPN, and further testing is ongoing [38].

10.8Conclusion

Keratoplasty has been the dominant therapy for rehabilitation of severely opaque corneas over the past century. However, limitations such as graft failure, poor prognosis in severe ocular surface disease, and high resource demands have fueled continued interest in

Kpro as a viable alternative to standard keratoplasty. Practical experience with Kpro has grown rapidly over the past few decades, and has brought forth key lessons in this evolving field. It is clear that diagnosis is a key determinant of prognosis, and that patients should be separated into two different categories based on the presence or absence of underlying inflammation. Recognition of these principles allows the promise of Kpro to emerge in the treatment of a large number of patients suffering from repeat graft failures. Patients with severe ocular surface disease from autoimmune conditions and chemical burns continue to challenge Kpro practitioners and researchers alike. The use of autologous biologic haptics as in OOKP and TKP shows promise for long-term device retention in cases of severe ocular surface disease, but may place greater demands on patients and practitioners. New directions in Kpro research will likely introduce biologically active materials into the clinical arena.

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Core Messages

■Posterior lamellar keratoplasty (PLK) offers many substantial benefits compared to penetrating keratoplasty (PK) including: closed eye surgery, elimination of both regular and irregular postoperative astigmatism leading to full visual rehabilitation with spectacles within 3-6 months, elimination of postoperative corneal anaesthesia, and a reduced risk of postoperative globe rupture.

■Disadvantages of PLK compared to PK include: corneal stromal scarring is untreatable by PLK,

complex anterior segment reconstruction is more difficult with PLK, PLK often fails in patients with aphakia and/or an incomplete lens iris diaphragm, early donor dislocation in PLK remains a problem.

■PLK techniques, and the indications for it, are still evolving.

■PLK is rapidly replacing PK as the procedure of choice for patients with otherwise uncomplicated endothelial cell loss such as pseudophakic bullous keratopathy and Fuchs’ endothelial dystrophy.

11.1Introduction

Endothelial dysfunction is a leading indication for corneal grafting. Although selective replacement of the dysfunctional endothelium is the logical approach, the procedure of choice, for over 100 years, has been penetrating (full thickness) keratoplasty. However penetrating keratoplasty leads to a variety of postoperative complications that burden the outcome, including high and/or irregular astigmatism, a long rehabilitation time, suture related complications, graft rejection and late wound dehiscence following trauma.

Posterior lamellar keratoplasty (PLK) as a selective replacement of posterior stroma and endothelium, was performed for the first time in humans by Tillett in 1956 [1]. Decades later, Melles described a sutureless corneal surgical technique for PLK, having done the first human case in 1998 [2, 3]. Terry and Ousley later modified this procedure and popularised it as deep lamellar endothelial keratoplasty (DLEK) performing their first case in 2000 [4].

Further modification of the technique, called small-inci- sion DLEK, enabled the surgeon to introduce the donor material through an opening as small as 5 mm [5].

Since then the technique has been simplified by Melles with the elimination of the deep lamellar dissection, required by DLEK, being replaced by the scoring and stripping of the host Descemet’s membrane and endothelium [6, 7] known as Descemet-stripping endothelial keratoplasy (DSEK). The combination of DSEK with the use of the automated microkeratome for donor preparation [8], instead of manual deep lamellar dissection, has resulted in the technique of Descemet-stripping automated endothelial keratoplasty (DSAEK). The ease of use of DSEK and DSAEK, which eliminate many of the disadvantages of penetrating keratoplasty, are responsible for the increasing use of PLK by corneal surgeons. In the United States alone, more than 14,000 corneas were provided by US eye banks for PLK in 2007, as compared with 1,400 corneas in 2005 (Eye Bank Association of America 2007 Eye Banking Statistical Report).

Descemet’s membrane endothelial keratoplasty (DMEK) in which Descemet’s membrane alone, without any supporting stromal tissue, is transplanted is currently

experimental [9, 10].

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11.2Choosing Endothelial Keratoplasty Procedures

11.2.1Indications

Endothelial dysfunction is one of the most frequent indications for corneal transplant surgery, varying from 12 to 60% of all transplant procedures in different series [11–14]. Table 11.1 summarises the most common causes of endothelial dysfunction, dividing them into primary endothelial dysfunctions, in which there is no established extrinsic precipitating cause as in the dystrophies, or endothelial dysfunctions secondary to extrinsic insults such as trauma, glaucoma, previous surgery or intraocular inflammation.

Th e recent update from the The Australian Corneal Graft Registry (ACGR), which covers all registry data from 1985–2006, reveals that out of more than 17,000 corneal grafts, bullous keratopathy (26%) follows keratoconus (32%) as a leading indication of keratoplasty. Other causes of endothelial dysfunction such as Fuchs’ dystrophy (6%), or decompensated corneal transplants (14%) also account for a substantial proportion of cases needing keratoplasty [15].

Table 11.1 Causes of corneal endothelial dysfunction

aNo established extrinsic precipitating cause for endothelial dysfunction

bEndothelial dysfunctions secondary to extrinsic insults

In our practice endothelial keratoplasty has become one of the most commonly performed transplant procedures, accounting for around 40% of cases; including Fuchs’ dystrophy, bullous keratopathy, and corneal graft failure.

11.2.2Preoperative Considerations

All corneal transplant surgery demands the preoperative assessment of the underlying cause of the corneal opacity, any comorbidity including the visual potential and the presence of cataract or lens implant function. For posterior keratoplasty additional considerations, that are less relevant to penetrating keratoplasty, are the degree of stromal scarring, any requirement for anterior segment reconstruction, and the integrity of the lens iris diaphragm which will influence the success of the current air bubble techniques for facilitating the attachment of posterior lamellar grafts.

11.2.2.1Confirming the Extent

of Endothelial Dysfunction

Th ere are several approaches for the evaluation of endothelial function:

■Visual symptoms. Blurred vision on waking that improves during the course of the day suggests endothelial failure.

■Morphological evaluation:

●Slit lamp: Gross or microcystic epithelial oedema is often present except in very early cases. Bilateral corneal guttata indicate Fuchs’ dystrophy as the cause of the disease.

●Specular microscopy: endothelial imaging with a range of specular microscopes can assess the morphology, size and density of the endothelial cells as well as identify guttata. However when the epithelium and stroma are opaque (due to oedema or scarring) the images are often too poor for meaningful analysis. This is also the case when there are dense guttata as these mask the underlying endothelial cells.

●Confocal microscopy: this permits easier imaging in the presence of corneal opacity. Guttata appear as hyporreflective images with occasional central bright images. Neither specular nor confocal microscopy assess endothelial cell pump function or the integrity of the intercellular tight junctions.

However normal endothelial cell morphology appears to be closely associated with normal pump function.

■Functional evaluation:

●Ultrasound or optical pachymetry: Corneal thickness is an indirect measurement of endothelial function and is used as an index of severity of endothelial dysfunction. Some authors have used a pachymetry measurement of greater than 640 mm [16] to indicate that the risk of corneal decompensation is too high to carry out cataract surgery without combined corneal transplant surgery. However this presupposes that the risk of endothelial cell loss with cataract surgery has remained constant with the introduction of newer techniques, and that there is minimal individual variation in normal corneal pachymetry. However corneal pachymetry varies widely with sex, age and ethnic group [17–19] such that a corneal thickness of 640 mm does not indicate the same degree of endothelial cell dysfunction for a patient who had a normal baseline pachymetry of 600 mm compared to another with a normal baseline pachymetry of 490 mm. As a result we use serial pachymetry to assess progression of disease in an individual and only recommend combined cataract and keratoplasty in patients who have clearly developed corneal epithelial oedema.

●Recovery aft er occlusion test: The ability of the cornea to de-swell after overnight eye closure also reveals the quality of the endothelial function. It is not uncommon to see patients who describe early morning blurring of vision which does not correlate with reduced acuity, signs of corneal decompensation or abnormal pachymetry. In this situation the patient can apply a patch the evening before a clinic visit; removing the patch in clinic mimics the early morning situation and shows both increased corneal thickness by pachymetry and clinical signs of corneal decompensation in patients with clinically significant endothelial dysfunction.

11.2.2.2Corneal Scarring

Advanced corneal decompensation may lead to corneal epithelial hypertrophy and subepithelial, stromal or pre-Descemet’s corneal scarring. Corneal epithelial hypertrophic membranes can be peeled off to reveal whether or not there is significant subepithelial fibrosis.

The extent of stromal and pre-Descemet’s scarring can be assessed with anterior segment ocular coherence tomography (OCT). Stromal scarring is a relative contraindication to endothelial keratoplasty in which the benefits of the procedure may be outweighed by the potential reduction in acuity.

11.2.2.3Cataract and Intraocular Lens Status

Cataract status in phakic patients can be difficult to assess in the presence of corneal decompensation. Because of the loss of endothelial cells associated with cataract surgery post keratoplasty, the predictability of the biometry with posterior lamellar grafts, the delay of 3 months to ensure posterior graft stability that is recommended before carrying out cataract surgery after endothelial keratoplasty, and the relative difficulty of phakic posterior keratoplasty, cataract surgery is commonly combined with PLK in post presbyopic patients and when there is a preexisting history of cataract [20].

For patients having combined cataract surgery and PLK the intraocular lens power chosen should take into account the hypermetropic shift of about +1 diopter [21, 22]. This is thought to be due to the curved configuration of the donor cornea when attached to the posterior host cornea, functioning as a negative lens, inducing 1D of myopia. As a result, for postoperative emmetropia, we use an estimated postoperative refraction of −1D when carrying out combined cataract surgery and endothelial keratoplasty [23].

Th e centration and condition of any intraocular lens must be assessed before PLK. Lens exchange is technically more difficult through a small incision than open sky in penetrating keratoplasty and the requirement for this may be a contraindication to PLK. An anterior chamber (AC) IOL is a relative contraindication to a PLK because of endothelial trauma during insertion, intermittent postoperative IOL touch, reduced depth of the AC and the difficulty of maintaining an air bubble in front of the IOL during DSEK/DSAEK [24]. To overcome this problem, it is possible to remove AC IOL’s at the time of PLK and replace these 3 months after a successful PLK or combine, in a single procedure, the replacement of the AC IOL with a scleral-fixated posterior chamber IOL [25].

11.2.2.4Lens/Iris Diaphragm Status

Th e current technique for donor attachment in DSEK/ DSAEK utilises an air bubble, usually under pressure, in the AC at the end of surgery.

In patients with aniridia, aphakia, iris defects, peripheral iris adhesions, and AC intraocular lenses, this is more difficult to achieve. In aphakic patients or those with a large iridotomy an AC air bubble may be difficult to

11 achieve at all, or move into the posterior segment, as soon as the, patient lifts their head, eliminating support for the posterior graft. Success rates can be improved at the time of PLK surgery by closing those defects that can be closed and by implanting a posterior chamber lens. The surgeon and the patient needs to be aware that failure in these situations is more likely; an air bubble retention test, before cutting the donor for PLK can eb helpful before makin a final decision about whether to proceed with a PK or PLK. Some surgeons advocate performing DLEK in such cases, as it is less dependent on the maintenance of a postoperative air bubble for graft adherence [26]; we have no experience with this technique.

11.2.2.5Intraocular Pressure

Failure to control intraocular pressure (IOP) after surgery reduces the survival of all types of corneal graft including PLK [27]. Normalising the IOP preoperatively is essential and we rarely proceed with graft surgery in patients requiring more than one topical hypotensive medication for good pressure control. In those with more severe glaucoma drainage surgery, usually with a tube, is carried out 3 months before graft surgery. Even in patients with advanced glaucoma an intraoperative pressure of 30 mmHg for 8 min is notanticipatedtoprejudiceopticnervefunction.Penetrating keratoplasty is known to have a detrimental effect on IOP [28], possibly because of altered post operative AC angle configuration which may be eliminated in PLK; it remains to be seen whether PLK has the anticipated neutral effect on IOP, although a small series of 44 patients with DLEK has shown that glaucoma may occur de novo in 7% of the patients [29] although some of these may be steroid related.

11.2.2.6Retinal Function

An estimate of postoperative acuity must be made before graft surgery. In patients with opaque media we find the previous history and clinical techniques, such as the assessment of pupil responses and ability to project light of more value than electrodiagnostic tests.

11.3PLK Surgical Technique

Currently Descemet stripping techniques by DSEK or DSAEK, rather than DLEK or DMEK, are the most widely used and this perspective will focus on these techniques. Surgery may be performed under all types of anaesthesia;

we prefer the use of local anaesthesia, such as a subtenons anaesthetic injection, to ensure that the patient can cooperate with face up posturing to maintain the air bubble in contact with the transplant in the immediate postoperative period.

11.3.1Donor Preparation

Donor dissection can be done manually (DSEK) or with a microkeratome (DSAEK). Microkeratome preparation causes a relatively small loss of endothelial cells, a more reproducible donor thickness and a smoother interface, decreasing visual recovery time and a decreased incidence of interface haze [8].

■Manual dissection of the donor is done using an artificial chamber such as Barron´s artificial chamber (Katena, Denville, NJ). Using an AC air bubble to estimate the depth of the dissection as described by Melles [30] is useful but not mandatory to achieve the appropriate depth and many do not use it. We aim for a two thirds depth donor dissection. Once dissection is complete the donor is punched on a block with the desired size trephine.

■Automated donor dissection is usually performed using the Moria automated anterior lamellar keratoplasty (ALTK) system (Moria, Antony, France). When intraoperative pachymetry is available we use the 350 mm head in donors measuring >570 mm and the 300 mm head for thinner donors. When pachymetry is not available we use the 350 mm head for cold stored material and the 300 mm head for deturgesced organ cultured donors. For the Amadeus II microkeratome (Ziemer Ophthalmic Systems AG, Switzerland) the recommendation is to use the 400 mm head [31]. Automated dissection has also been effectively performed using femtosecond laser (IntraLase Corp, Irvine, CA) with no detrimental effect on endothelial cell density in eye bank eyes. Femtosecond laser lamellar dissection seemed to be less deep and less smooth [32]. Preliminary results of femtosecond laser-assisted descemet stripping endothelial keratoplasty in 20 patients showed limited improvement of BSCVA, with higher endothelial cell loss, hyperopic shift and dislocation rate than expected for ALTK dissection [33].

11.3.2Host Dissection for DSEK/DSAEK

Our current technique is as follows:

■Lightly mark the epithelium with gentian violet using a 7.5 mm circular marker touched onto a gentian violet pad, we aim for a descemethorrexis of about 7.5 mm

that is 0.5–1.0 mm less in diameter than the size of the donor to avoid removing host Descemet’s outside the donor graft site.

■Create a 5 mm temporal corneal OR scleral tunnel.

■Either use a peripherally placed self retaining infusion (Lewicky cannula) to maintain the AC or a cohesive viscoelastic while removing Descemet’s. We prefer to use a cannula as it also helps to maintain the AC during the insertion of the graft (see below). If the cannula is used it is important to keep bottle height low to reduce the risk of iris prolapse which tends to recur thereafter. Persistent iris prolapse can be managed by the insertion of an IOL glide.

■Perform one or two small vertical peripheral paracenteses (outside the zone of graft) to permit air injection after graft insertion.

■Delineate the area of Descemetorhexis with a reverse

(upturned) Sinskey hook (Moria, Antony, France) and use this, a Paufique knife or a Descemet’s stripper (Moria, Antony, France) to remove Descemets. “Roughing up” the peripheral stroma with the reverse Sinskey, or a Terry Scraper (Bausch and Lomb, St. Louis, MO) may help adhesion [34].

11.3.3Donor Insertion

Th ere are several current methods in use for the introduction of the donor including forceps insertion (“taco” technique) [35], pull through [36] and glide techniques [37]. The forceps technique (Fig. 11.1a) was the first described of these, and may be the most widely used, however there have been concerns about the effect of forceps induced endothelial crush injury, as well as handling difficulties, especially when the donor lenticule is thin, which the pull through and glide techniques were introduced to address.

■Suture guided pull through technique (Fig. 11.1c, d): A 10–0 polypropylene suture (Prolene; Ethicon, San Angelo, Texas, USA) on a long straight needle (STC-6, Ethicon) is passed partial thickness through the edge of the cornea and tied with an overhand knot to create a loop. The length of the loop is made large enough to allow it to be cut after the donor is placed. The straight needle is passed through the incision and across the anterior chamber and out again through the cornea at 180° opposite the incision. It is important to ensure that the needle does not pass through tissue at the incision site which will prevent the graft passing into the eye. The donor, after coating the endothelium with cohesive viscoelastic, is placed in the wound entrance either folded, or unfolded with the endothelium side

down. The donor is then drawn into the AC by drawing on the suture or is held there if the technique is forceps assisted. An AC maintainer is used to maintain the AC during insertion. We prefer not to use forceps assisted insertion as the cornea may be difficult to grasp, causing trauma, and can unfold endothelium uppermost which is unlikely to occur when the donor is pulled through endothelial side down.

■Busin glide (ref. 19,098, Moria SA, Anthony, Francia) guided pull through technique (Fig. 11.1b): The donor tissue is placed on the glide with the endothelium facing upward. The glide is then turned over and pushed against the entrance of the incision or into the AC. The cornea is pulled from one edge into the AC using crocodile vitreoretinal forceps that is inserted through a paracentesis opposite the main wound.

■Other glides/injectors: these have been reported but are not yet commercially available.

11.3.4Techniques for Graft Centration

Once the donor cornea is in the AC and correctly oriented, the pull through suture is removed, any infusion removed and all wounds closed to be both air and watertight. An air bubble is injected under the corneal donor to hold it against the host posterior stroma. There are several techniques that can be used to position the donor. These work best at normal levels of IOP.

■Corneal “balloting” (Fig. 11.2a): in which the surface of the host cornea overlying the edge of the graft away from the desired direction of movement is firmly indented and swept towards the desired position with a blunt instrument such as a squint hook or the angled surface of a 20 gauge angled cannula [38].

■Corneal centration using a hook (Fig. 11.2b): the tip of an insulin syringe can be bent like a reverse capsulotomy needle and introduced through side port to engage the edge of the endothelial surface of the donor and pull the graft into position [38]. This results in loss of the AC air and fluid and is more traumatic than the transcorneal needle technique.

■Corneal centration using a transcorneal needle (Fig. 11.2c): a long fine needle such as the 10–0 polypropylene suture needle used for the pull through technique (Prolene, Ethicon, San Angelo, Texas, USA). The fine needle is pushed at an angle through the periphery of the host cornea to engage the stromal surface of the donor and push it into position. We use this when the cornea does not respond to “balloting”.

11.3.5Techniques for Promoting Donor Adhesion

Several strategies have been advocated to improve corneal adhesion. The most effective are:

■Peripheral roughening of the host posterior stroma immediately after performing the descemetorrhexis [39].

■Sweep and compress the cornea using a blunt instrument such as an 20 guage cannula or a roller from the centre to the periphery to “milk” any interface fluid out to the edge of the graft and into the AC to ensure stroma to stroma surface contact [7].

■Place four slightly bevelled stab incisions from the surface to the interface in the pericentral zone

using a 1-mm wide diamond paracentesis knife [7]. Fill the AC completely with air ensuring that the donor is fully in contact with the host cornea. The edge of the donor is visible as a refractile ring when this is achieved. Ideally ensure the pressure is between 30–50 mmHg with a tonometer and maintain this for 8–10 min in the operating theatre; then remove enough air to soften the eye but leave a bubble in the AC. Some authors recommend an inferior ocutome iridotomy (performed at the time of the descemetorhexis) to reduce the risk of pupil block [40].

■Posture the patient face up for a period of time immediately after surgery to use the AC air to maintain the donor in position [8]. We currently recommend this for 1 h.

11.3.6Post-operative Care

After the period of face up posturing the patient is fully mobilised and examined to exclude the development of pupil block [8].

■If pupil block is present air can be easily removed at the slit lamp with a 30 guage cannula via a preexisting superior paracentesis.

■Th e patient can then be fully mobilised and instructed to take special care not to rub the eye which may dislocate the donor in the early postoperative stages. We provide a clear cartela shield to be worn at night post surgery.

■We review the patient at 24 h and 7 days to ensure that the donor is adherent. If not immediate repositioning is carried out with repeat air tamponade.

■Single sutures closing paracenteses can be removed early.

■We remove sutures closing the corneal wound at 3 months.

■We use the same postoperative topical steroid and antibiotic regimen as for penetrating keratoplasty.

■Spectacles can be changed as early as a few weeks after surgery and the vision is usually approaching the final acuity at 3–6 months.

11.3.7Surgery for Complex Cases

11.3.7.1Failed Grafts

Patients with previous penetrating keratoplasty that has failed can also benefit from DSAEK (Fig. 11.3c, d). In the first published series of seven consecutive patients, all cases showed successful adherence of the donor button and cleared the edema from the previous penetrating graft. Best-corrected visual acuity had improved in

six of the seven cases compared with the preoperative vision at 3 months [41]. In another small series of seven cases with a mean follow up of 13 months, four of six eyes (67%) achieved a BCVA of 20/40 or better. One eye suffered recurrent donor graft dislocation and elected to undergo repeat PK instead of repeat DSAEK. The other six grafts remained clear at the last follow-up visit, although 2/6 needed repositioning and another 2/6 had primary iatrogenic graft failure within 1 week of DSAEK and underwent repeat DSAEK with new donor tissue with good results [42].

Th e technique is not much different to conventional DSAEK:

■Price et al [41], did not strip the Descemet membrane from the failed graft or recipient cornea before implant-

ing the donor tissue in five of the seven cases where preoperative examinations determined that there were no guttata and that the Descemet membrane had been clear before corneal decompensation. The donor cornea used was 8.5–9 mm, which was probably bigger than the previous penetrating keratoplasty button although not specified.

■Covert et al [42], stripped the host endothelium and Descemet membrane corresponding to the previous 8.0-mm keratoplasty incision, and the corneal lenticule inserted was 8.5 mm which was bigger than the previous PK donor button.

■We usually remove Descemet’s within the graft margins to avoid corneal dehiscence, and also make the donor larger than the previous graft by about 0.5–1 mm when possible.

11.3.7.2Aniridics, Vitrectomised

and Aphakic Eyes (Fig. 11.3e)

Maintenance of air is difficult in aphakic eyes in which there is no capsular bag to isolate the AC, increasing the risk of donor dislocation and failure after DSAEK. The main factor affecting a successful outcome in these cases is the ability to maintain air in the AC in the first postoperative hours in addition to strict face-up positioning [43]. Price and Price [44] described successful outcomes in two eyes with aphakic bullous keratopathy before DSEK with a simultaneous secondary IOL in one eye, and a secondary IOL implanted 4 months after DSEK in the other eye. A donor dislocation was successfully repositioned in one eye. Another study included three aphakic patients who underwent DSEK with varied results. Two of them had a favourable outcome using air injection in one case and longer-lasting gas (SF6) with higher buoyancy than air to fill the AC in the other case with broad iridectomy. The last patient had donor disc displaced posteriorly leading to total RD and no perception of light [43]. The use of long-lasting, higher-buoy- ancy gases could be a possible solution for these patients.

Price et al [43], have modify their technique for these cases:

■Descemet’s membrane was not stripped from the recipient eye.

■Th e stromal side of the donor tissue was stained with trypan blue to improve visualisation.

■Th e donor tissue was initially inserted only 80–90% of the way into the eye so that one end was held in the incision, while an anchor suture was placed in the peripheral edge of the anterior portion of the donor tissue to secure it to the overlying recipient cornea. This step can be avoided in our experience by using a pull through technique with a 10/0 prolene straight needle that secures the donor graft in the AC combined with a trailing suture, on the opposite side of the donor to hold it anteriorly, preventing dislocation posteriorly before injecting air.

■Air is not removed from the eye at the end of the case.

Some authors advocate the convenience of performing a DLEK with successful results [45] as described in 1.2.2.4 in cases where it is foreseen that the air bubble will not be retained in the AC. Placing a posterior chamber lens, closing all iris defects where possible and testing the eye for air retention before making a final decision a between PK and PLK can contribute to successful outcomes.

11.3.7.3Anterior Chamber Lens

Th is is explained in Sect. 1.2.2.3. See Fig. 11.3f.

11.4Clinical Results and Complications

Th e theoretical advantages and disadvantages of PLK compared to penetrating keratoplasty are summarised in Table 11.2.

11.4.1 Visual Acuity

A major concern about lamellar techniques is the creation of an interface that limits both visual acuity and quality of vision. However several studies [20, 21, 40, 46, 47] have shown that mean best corrected visual acuity in DSAEK ranges from 20/34 to 20/44 which is superior to the historical results of PK for similar indications (Fuchs’, pseudophakic and aphakic bullous keratopathy) [40, 47]. In a series of 100 cases, 72/74 (97%) of the eyes with corneal decompensation and no other comorbidity achieved BSCVA of 20/40 and up to 10/74 (14%) achieved BSCVA of 20/20 after 6 months [46]. Similar levels of visual acuity have also been achieved by other posterior lamellar techniques such as DSEK [7], and DLEK [35]. The unaided and spectacle corrected visual acuity that can be achieved with PLK, which eliminates the problem of regular and irregular astigmatism that are associated with PK, are the what makes the biggest difference to the visual outcomes when comparing the results of PLK with PK.

11.4.2Astigmatism

Induced astigmatism is not an issue after DSAEK. All the big series published so far have shown changes in mean refractive or topographic astigmatism of around 0.10 dioptres, which were not statistically significant from baseline [20, 21, 40, 46]. Similar results have been reported for DSEK [7] and DLEK techniques [35] with the exception of early cases of DLEK with a large incision of 9 mm [35]. All the endothelial keratoplasty techniques induce substantially less regular astigmatism when compared to penetrating keratoplasty [47] which also causes irregular astigmatism in some cases that requires contact lens correction for good vision [48].

11.4.3Spherical Equivalent

Th eoretically the placing of a donor corneal disc behind the host cornea posterior will steepen the posterior corneal curvature adding negative refractive power to this

interface. This effect will decrease the total corneal power causing a hyperopic shift [23]. This hyperopic shift after PLK has been identified in several case series and has resulted in a change of the mean spherical equivalent from +0.50 to +1.12 D [7, 20, 21, 40]. Adjustment for the effect of this postoperative hyperopic shift, in planned cataract and PLK surgery, can be made by selecting an IOL with more power than the IOL power estimate for cataract surgery alone. We aim for a postoperative target refraction of −1D.

11.4.4Endothelial Cell Loss

Th ere has been continuing concern about the potential for increased endothelial cell loss in PLK compared to PK as a result of the effects of the preparation, manipulation, and insertion of the donor disc.

■Some surgeons use a larger graft diameter for PLK than PK to potentially correct for this; a 9.0 mm diameter PLK provides 26% more endothelial cells than an 8.0 mm PK graft.

■Reports of endothelial cell loss have been very variable from as high as 50% at 6 months [21], to 26% after 2 years in the Busin series [37]. Other reports suggest

that there is no difference between cell loss with a 40% loss at 1 year for both PLK and PK [47] and a recent study comparing endothelial cell loss in historical PK vs. DSAEK, or other PLK techniques, showed no measurable difference [47].

■Th e insertion technique is likely to be an important determinant of endothelial cell loss and less traumatic techniques, such as the use of a glide, might reduce loss [49], although there are currently no definitive studies, no consensus, and techniques are still in evolution.

■Th e size of the wound, and its localisation (corneal vs. scleral), is also likely to have an effect with smaller corneal and scleral tunnel incisions increasing loss possibly due to compression of the donor graft during insertion [50, 51].

■A recent retrospective study showed that there was no statistical difference between forceps and pull through techniques (suture or glide guided) but that a 3 mm incision resulted in more endothelial cell loss than a 5 mm incision [52].

Further studies prospectively evaluating donor insertion protocols will establish the optimum techniques after which careful prospective comparative or randomised studies are needed to establish loss rates in PLK vs. PK.

11.4.5Corneal Donor Dislocation (Fig. 11.4a–c)

Th e mechanisms of donor tissue attachment in PLK surgery are not established. Early postoperative attachment is likely to involve a combination of physical, biochemical, and physiological processes [52]. Dispersive viscoelastics like Viscoat (Alcon, Fort Worth, TX) and hydroxypropyl methylcellulose and possibly retained Descemet’s membrane have been associated with dislocation [53]. However leaving host descemet’s membrane intact did not cause dislocations in patients with previous PK undergoing PLK in one case series case series [41].

Evidence for the efficacy of different techniques to aid attachment is based on the reports of success rates

a

c

e

in case series and not on experimental or prospective evaluation of different techniques. Section 1.3.5 summarises the methods most frequently described: using corneal massage, stab incisions, peripheral recipient bed roughening and high pressure with air tamponade in the AC (>30 mmHg) for 8–10 min. Donor dislocation is the most common complication of DSAEK surgery with reported rates varying from the lowest reported figure of 3/200 (1.5%) consecutive cases in which peripheral recipient bed scraping and sweeping of the corneal surface was used routinely [34] to 9/26 (35%) when the donor graft was positioned using a temporary air bubble that was partially evacuated after 7 min [40].

b

d

11.4.6Pupillary Block

Th is complication is caused by the AC air bubble which can occlude the pupil and cause angle closure resulting in 11 acute glaucoma, a flat AC, peripheral iris synechiae, iridocorneal adhesions, or a induced branch vein occlusion [40]

and Urrets-Zavalia syndrome. Preventive measures are:

■To review the patient 1–2 h after the surgery to exclude this and remove any excess air if necessary [40]. We do this for all cases.

■Make an inferior iridectomy (a superior iridectomy is more easily blocked by air) [40]. This is easily carried out at the start of the procedure with an ocutome cutter. We use this procedure for phakic cases in whom we miose the pupil with pilocarpine to reduce the risk of crystalline lens damage during donor insertion.

■Dilate the pupil with topical cyclopentolate 1% and phenylephrine 2.5% at the end of surgery.

■In pseudophakic patients AC volume is greater. Some surgeons recommend removing most of the air at the end of surgery, leaving enough to cover the edges of the donor, and ensuring that the bubble is mobile in the AC by moving the patients head from side to side to assess mobility [34]. We prefer to leave the AC full of air but with a soft eye and remove any excess 1–2 h after surgery via a paracentesis.

11.4.7Primary Graft Failure

Primary graft failure is uncommon after PK occurring at a rate of about 1:400 [34], but has been reported frequently after PLK particularly in surgeons early cases. Surgeons initial consecutive case series have reported primary failure as high as 3/34 (9%) [21] and 21/118 (18%) [54]; these high rates are likely to result from the surgeon learning curve with ten surgeons doing the 118 cases in the latter series. On the other hand some single surgeon series have reported no primary graft failures in his 200 DSAEK’s [34] and only 1/100 in the first 100 DSEK and DSAEK cases. The decreased incidence of primary graft failure with increased DSAEK surgeon experience suggests that primary graft failure in DSAEK is more likely to be related to endothelial trauma during the operative procedure rather than to problems with eye bank selection and storage. In addition primary graft failure is 5 times more common in grafts that needed a second surgical intervention to treat early dislocation [55] which is in turn related to case selection being more common in patients with preoperative lens/iris diaphragm deficiency and aphakia in whom the donor dislocation rate is double [55] (Fig. 11.4d).

However the similar rates of endothelial cell loss that have been reported for PK and PLK suggest that with good currently available techniques cell loss may be no greater in PLK than PK. It is likely that as insertion and attachment protocols, and surgeon training, are improved overall endothelial cell loss and primary graft failures will be no more for PLK than PK.

11.4.8Rejection

One series of 199 eyes, having had DSAEK or DLEK, and a follow up of 2 years had a rejection rate of 15/199 (7.5%) compared to a rate of 92/708(13%) in a historical case series of PK’s carried out for similar indications [56]. In addition the morbidity following rejection was less severe in the PLK series with only 6.7% proceeding to graft failure compared to 28.3% of the PK’s. However 80% of the PLK patients were still taking topical steroid medication 2 years after surgery whereas this had been stopped 1 year after surgery in the PK patients and this may have accounted for the difference rather than any potential reduction in antigenicity due to the reduced bulk of the PLK. That steroid may well have been a confounding factor in this study is suggested by the findings of a recent randomised controlled trial of topical steroid vs. no topical steroid after PK in which the topical steroid was discontinued 6 months post op in one group and continued for 12 months in the second group resulting in a 50% reduction in the rate of rejection (19/202 (9.1%) in the no steroid group vs. 10/204 (4.9%) in the topical steroid group) [57]. PLK rejection rates reported from other studies are 7/118 (6%) DSAEK’s [54] in which the mean follow up was uncertain. In the largest published study by Price et al, graft rejection occurred in 54/598 (9%) eyes after Descemet stripping with endothelial keratoplasty [58]. Thirty-five per cent of the eyes were asymptomatic and were diagnosed during routine examination. Signs of immunological rejection at the initial diagnosis included keratic precipitates (69%), diffuse corneal oedema (11%) or both (20%); no endothelial rejection lines were observed [58].

11.4.9Other Complications

Other complications of DSAEK are cystoid macular edema [54], interface opacities [54] (Fig. 11.4e), retinal detachment [54], suprachoroidal haemorrhage [54], donor dislocation into the posterior segment [54] and dislocation of an intraocular lens into the vitreous cavity as a consequence of the increase in AC volume during air tamponade [59].

11.5Conclusion

Th is perspective shows that an experienced surgeon, operating on patients with corneal endothelial disease, such as Fuchs’ dystrophy or pseudophakic bullous keratopathy (PBK), can expect to obtain more predictable results, much more quickly, with PLK than with PK and with fewer postoperative complications, particularly those relating to astigmatism, sutures and resistance to trauma. Following PLK using DSAEK or DSEK most patients can expect to achieve vision that is adequate for them to meet the driving standard within 3 months, using spectacles. Combined cataract and PLK surgery works well also. We believe that PLK will rapidly supersede PK for this patient group in the same way that phacoemulsification has replaced large incision extracapsular cataract extraction for most cataract patients.

However there remain many areas where the role of this technique is uncertain. It can provide excellent results for restoration of corneal clarity in patients with failed PK. It can also succeed in patients with AC lenses although success is uncertain in this situation. It can be difficult, or impossible, to do DSAEK or DSEK when an air bubble cannot be retained in the AC as can happen in some patients with a deficiency in the lens iris diaphragm. In patients with some stromal opacity PLK may still be a better option than PK, with less risk, even though the visual outcome may be compromised by corneal stromal opacification and in whom residual superficial stromal opacity can be treated with an excimer laser phototherapeutic keratectomy. Because of the difficulty of access to lens and iris structures through a small incision patients requiring lens exchange and/or pupilloplasty may be better having a conventional PK. Prospectively collected data on the use of PLK for complex and high risk cases will answer many of the questions raised in this perspective and the risks and benefits of the technique will be clarified in the next few years.

PLK is also an evolving technique with regard to the success of protocols for ensuring donor graft adhesion in DSEK and DSAEK. Prospective case series can be expected to clarify the optimal techniques for this and, like all new surgical procedures, a stable and effective solution will be developed in time. Meanwhile refinements to the procedure, including the development of DMEK, can be expected to improve the already remarkable visual results available using DSAEK and DSEK.

Lamellar corneal procedures promise to replace PK as the procedure of choice for corneal replacement surgery except for corneal disease involving both stroma and endothelium and for therapeutic procedures.

References

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340–341

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